Study of ARO-AAT in Normal Adult Volunteers
Primary Purpose
Alpha 1-Antitrypsin Deficiency
Status
Completed
Phase
Phase 1
Locations
New Zealand
Study Type
Interventional
Intervention
ARO-AAT Injection
Sterile Normal Saline (0.9% NaCl)
Sponsored by
About this trial
This is an interventional treatment trial for Alpha 1-Antitrypsin Deficiency
Eligibility Criteria
Inclusion Criteria:
- Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
- Willing to provide written informed consent and to comply with study requirements
- Non-smoker for at least one year
- Normal lung function
- No abnormal finding of clinical relevance at Screening
- Normal AAT level at Screening visit
Exclusion Criteria:
- Clinically significant health concerns
- Regular use of alcohol within one month prior to Screening
- Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
- Recent use of illicit drugs
- Use of any drugs or dietary/herbal supplements know to interfere with liver metabolism
NOTE: additional inclusion/exclusion criteria may apply, per protocol
Sites / Locations
- Auckland Clinical Studies Limited
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
ARO-AAT
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment
Secondary Outcome Measures
Pharmacokinetics (PK) of ARO-AAT: Maximum Observed Plasma Concentration (Cmax)
PK of ARO-AAT: Time to Maximum Plasma Concentration (Tmax)
PK of ARO-AAT: Terminal Elimination Half-Life (t½)
PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
Percent Change in Serum Alpha-1 Antitrypsin (AAT) Levels From Day 1 Pre-Dose Baseline to Nadir
Duration of Response of Serum AAT levels From Nadir Back to Above 20% of Baseline or Above 90 mg/dL
Full Information
NCT ID
NCT03362242
First Posted
November 30, 2017
Last Updated
August 17, 2020
Sponsor
Arrowhead Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03362242
Brief Title
Study of ARO-AAT in Normal Adult Volunteers
Official Title
A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Effect of ARO-AAT on Serum Alpha-1 Antitrypsin Levels in Normal Adult Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
March 12, 2018 (Actual)
Primary Completion Date
October 23, 2018 (Actual)
Study Completion Date
March 21, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-AAT in healthy adult volunteers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha 1-Antitrypsin Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARO-AAT
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ARO-AAT Injection
Intervention Description
Single or multiple doses of ARO-AAT by subcutaneous (sc) injections
Intervention Type
Other
Intervention Name(s)
Sterile Normal Saline (0.9% NaCl)
Intervention Description
Calculated volume to match active comparator
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment
Time Frame
Part A (single-ascending dose [SAD] phase): up to 29 (+/- 2) days post-dose; Part B (multiple-ascending dose [MAD] phase): up to 113 (+/- 2) days post-dose
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of ARO-AAT: Maximum Observed Plasma Concentration (Cmax)
Time Frame
Part A (single-ascending dose [SAD] phase): up to 48 hours post-dose; Part B (multiple-ascending dose [MAD] phase): up to 48 hours post-dose
Title
PK of ARO-AAT: Time to Maximum Plasma Concentration (Tmax)
Time Frame
Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
Title
PK of ARO-AAT: Terminal Elimination Half-Life (t½)
Time Frame
Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
Title
PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
Time Frame
Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
Title
PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
Time Frame
Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
Title
Percent Change in Serum Alpha-1 Antitrypsin (AAT) Levels From Day 1 Pre-Dose Baseline to Nadir
Time Frame
Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days
Title
Duration of Response of Serum AAT levels From Nadir Back to Above 20% of Baseline or Above 90 mg/dL
Time Frame
Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
Willing to provide written informed consent and to comply with study requirements
Non-smoker for at least one year
Normal lung function
No abnormal finding of clinical relevance at Screening
Normal AAT level at Screening visit
Exclusion Criteria:
Clinically significant health concerns
Regular use of alcohol within one month prior to Screening
Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
Recent use of illicit drugs
Use of any drugs or dietary/herbal supplements know to interfere with liver metabolism
NOTE: additional inclusion/exclusion criteria may apply, per protocol
Facility Information:
Facility Name
Auckland Clinical Studies Limited
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1010
Country
New Zealand
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of ARO-AAT in Normal Adult Volunteers
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